Correlation between small-scale methylation changes and gene expression during the development of myopia.

Visually induced changes in the expression of early growth response-1 (EGR1), FBJ osteosarcoma oncogene (FOS), and NGFI-A binding protein-2 (NAB2) appear to form a part of a retinal network fundamental to ocular growth regulation, and thus, the development of myopia (short-sightedness). However, it is unclear how environmental (visual) cues are translated into these molecular changes. One possibility is through epigenetic modifications such as DNA methylation, a known regulator of such processes. By sequencing bisulfite-converted DNA amplicons, this study examined whether changes in DNA methylation occur within specific regulatory and promoter regions of EGR1, FOS, and NAB2 during the periods of increased and decreased ocular growth in chicks. Visually induced changes in ocular growth rates were associated with single-point, but not large-scale, shifts in methylation levels within the investigated regions. Analysis of methylation pattern variability (entropy) demonstrated that the observed methylation changes are occurring within small subpopulations of retinal cells. This concurs with previous observations that EGR1 and FOS are differentially regulated at the peptide level within specific retinal cell types. Together, the findings of this study support a potential role for DNA methylation in the translation of external visual cues into molecular changes critical for ocular growth regulation and myopia development.

Time outdoors positively associates with academic performance: a school-based study with objective monitoring of outdoor time.

BACKGROUND: To explore the relationship between outdoor time and academic performance among school-aged children. METHODS: This study was designed as a cross-sectional study. Data were derived from a school-based prospective children myopia intervention study (STORM). Outdoor time was recorded by self-developed algorithm-validated wristwatches in real-time and calculated as the cumulative average of 10 months. The academic performance was recorded and provided by the participating schools and further standardized. Other information was collected using an online standardized questionnaire. Mixed-effects model and B-Spline method were used to investigate the association between time spent on different types of daily activity, including outdoor activity and academic performance. RESULTS: A total of 3291 children with mean age 9.25 years were included in the final analysis. Overall, outdoor time was associated with academic performance in a non-linear manner; specifically, not exceeding 2.3 h per day, outdoor time was positively associated with academic performance; exceeding 2.3 h per day, this association became non-significant. Likewise, daily sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner, resulting in turning points of 11.3 and 1.4 h per day, respectively. Separate analysis showed that outdoor time and sleep duration but not out-of-school learning time were positively associated with academic performance in Chinese, mathematics and English. CONCLUSION: Outdoor time, sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner. Promotion of outdoor time may not negatively impact on academic performance. TRIAL REGISTRATION: Our study was registered in ClinicalTrials.gov (Identifier: NCT02980445).

Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children: A Multicenter Randomized Controlled Trial.

PURPOSE: To assess the efficacy and safety of repeated low-level red-light (RLRL) therapy in myopia control in children. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial. PARTICIPANTS: Two hundred sixty-four eligible children 8 to 13 years of age with myopia of cycloplegic spherical equivalent refraction (SER) of -1.00 to -5.00 diopters (D), astigmatism of 2.50 D or less, anisometropia of 1.50 D or less, and best-corrected visual acuity (BCVA) of 0.0 logarithm of the minimum angle of resolution or more were enrolled in July and August 2019. Follow-up was completed in September 2020. METHODS: Children were assigned randomly to the intervention group (RLRL treatment plus single-vision spectacle [SVS]) and the control group (SVS). The RLRL treatment was provided by a desktop light therapy device that emits red light of 650-nm wavelength at an illuminance level of approximately 1600 lux and a power of 0.29 mW for a 4-mm pupil (class I classification) and was administered at home under supervision of parents for 3 minutes per session, twice daily with a minimum interval of 4 hours, 5 days per week. MAIN OUTCOME MEASURES: The primary outcome and a key secondary outcome were changes in axial length and SER measured at baseline and the 1-, 3-, 6-, and 12-month follow-up visits. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy based on a longitudinal mixed model. RESULTS: Among 264 randomized participants, 246 children (93.2%) were included in the analysis (117 in the RLRL group and 129 in the SVS group). Adjusted 12-month axial elongation and SER progression were 0.13 mm (95% confidence interval [CI], 0.09-0.17mm) and -0.20 D (95% CI, -0.29 to -0.11D) for RLRL treatment and 0.38 mm (95% CI, 0.34-0.42 mm) and -0.79 D (95% CI, -0.88 to -0.69 D) for SVS treatment. The differences in axial elongation and SER progression were 0.26 mm (95% CI, 0.20-0.31 mm) and -0.59D (95% CI, -0.72 to -0.46 D) between the RLRL and SVS groups. No severe adverse events (sudden vision loss ≥2 lines or scotoma), functional visual loss indicated by BCVA, or structural damage seen on OCT scans were observed. CONCLUSIONS: Repeated low-level red-light therapy is a promising alternative treatment for myopia control in children with good user acceptability and no documented functional or structural damage.

Time Outdoors in Reducing Myopia: A School-Based Cluster Randomized Trial with Objective Monitoring of Outdoor Time and Light Intensity.

PURPOSE: To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift. DESIGN: A prospective, cluster-randomized, examiner-masked, 3-arm trial. PARTICIPANTS: A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group. METHODS: An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up. MAIN OUTCOME MEASURES: The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years. RESULTS: The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%～ 24%. CONCLUSIONS: Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect.

Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study.

BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.

Increased Time Outdoors Is Followed by Reversal of the Long-Term Trend to Reduced Visual Acuity in Taiwan Primary School Students.

PURPOSE: To investigate the change in the prevalence of reduced visual acuity (VA) in Taiwanese school children after a policy intervention promoting increased time outdoors. DESIGN: Prospective cohort study based on the Taiwan School Student Visual Acuity Screen (TSVAS) by the Ministry of Education in Taiwan. PARTICIPANTS: All school children from grades 1 through 6 were enrolled in the TSVAS from 2001 through 2015. METHODS: The TSVAS requires each school in Taiwan to perform measurements of uncorrected VA (UCVA) on all students in grades 1 through 6 every half year using a Tumbling E chart. Reduced VA was defined as UCVA of 20/25 or less. Data from 1.2 to 1.9 million primary school children each year were collected from 2001 through 2015. A policy program named Tian-Tian 120 encouraged schools to take students outdoors for 120 minutes every day for myopia prevention. It was instituted in September 2010. To investigate the impact of the intervention, a segmented regression analysis of interrupted time series was performed. MAIN OUTCOME MEASURES: Prevalence of reduced VA. RESULTS: From 2001 to 2011, the prevalence of reduced VA of school children from grades 1 through 6 increased from 34.8% (95% confidence interval [CI], 34.7%-34.9%) to 50.0% (95% CI, 49.9%-50.1%). After the implementation of the Tian-Tian 120 outdoor program, the prevalence decreased continuously from 49.4% (95% CI, 49.3%-49.5%) in 2012 to 46.1% (95% CI, 46.0%-46.2%) in 2015, reversing the previous long-term trend. For the segmented regression analysis controlling for gender and grade, a significant constant upward trend before the intervention in the mean annual change of prevalence was found (+1.58%; standard error [SE], 0.08; P < 0.001). After the intervention, the trend changed significantly, with a constant decrease by -2.34% annually (SE, 0.23; P < 0.001). CONCLUSIONS: Policy intervention to promote increased time outdoors in schools was followed by a reversal of the long-term trend toward increased low VA in school children in Taiwan. Because randomized trials have demonstrated outdoor exposure slowing myopia onset, interventions to promote increased time outdoors may be useful in other areas affected by an epidemic of myopia.

Prediction of myopia development among Chinese school-aged children using refraction data from electronic medical records: A retrospective, multicentre machine learning study.

BACKGROUND: Electronic medical records provide large-scale real-world clinical data for use in developing clinical decision systems. However, sophisticated methodology and analytical skills are required to handle the large-scale datasets necessary for the optimisation of prediction accuracy. Myopia is a common cause of vision loss. Current approaches to control myopia progression are effective but have significant side effects. Therefore, identifying those at greatest risk who should undergo targeted therapy is of great clinical importance. The objective of this study was to apply big data and machine learning technology to develop an algorithm that can predict the onset of high myopia, at specific future time points, among Chinese school-aged children. METHODS AND FINDINGS: Real-world clinical refraction data were derived from electronic medical record systems in 8 ophthalmic centres from January 1, 2005, to December 30, 2015. The variables of age, spherical equivalent (SE), and annual progression rate were used to develop an algorithm to predict SE and onset of high myopia (SE ≤ -6.0 dioptres) up to 10 years in the future. Random forest machine learning was used for algorithm training and validation. Electronic medical records from the Zhongshan Ophthalmic Centre (a major tertiary ophthalmic centre in China) were used as the training set. Ten-fold cross-validation and out-of-bag (OOB) methods were applied for internal validation. The remaining 7 independent datasets were used for external validation. Two population-based datasets, which had no participant overlap with the ophthalmic-centre-based datasets, were used for multi-resource validation testing. The main outcomes and measures were the area under the curve (AUC) values for predicting the onset of high myopia over 10 years and the presence of high myopia at 18 years of age. In total, 687,063 multiple visit records (≥3 records) of 129,242 individuals in the ophthalmic-centre-based electronic medical record databases and 17,113 follow-up records of 3,215 participants in population-based cohorts were included in the analysis. Our algorithm accurately predicted the presence of high myopia in internal validation (the AUC ranged from 0.903 to 0.986 for 3 years, 0.875 to 0.901 for 5 years, and 0.852 to 0.888 for 8 years), external validation (the AUC ranged from 0.874 to 0.976 for 3 years, 0.847 to 0.921 for 5 years, and 0.802 to 0.886 for 8 years), and multi-resource testing (the AUC ranged from 0.752 to 0.869 for 4 years). With respect to the prediction of high myopia development by 18 years of age, as a surrogate of high myopia in adulthood, the algorithm provided clinically acceptable accuracy over 3 years (the AUC ranged from 0.940 to 0.985), 5 years (the AUC ranged from 0.856 to 0.901), and even 8 years (the AUC ranged from 0.801 to 0.837). Meanwhile, our algorithm achieved clinically acceptable prediction of the actual refraction values at future time points, which is supported by the regressive performance and calibration curves. Although the algorithm achieved balanced and robust performance, concerns about the compromised quality of real-world clinical data and over-fitting issues should be cautiously considered. CONCLUSIONS: To our knowledge, this study, for the first time, used large-scale data collected from electronic health records to demonstrate the contribution of big data and machine learning approaches to improved prediction of myopia prognosis in Chinese school-aged children. This work provides evidence for transforming clinical practice, health policy-making, and precise individualised interventions regarding the practical control of school-aged myopia.

Significant Axial Elongation with Minimal Change in Refraction in 3- to 6-Year-Old Chinese Preschoolers: The Shenzhen Kindergarten Eye Study.

PURPOSE: To document the distribution of ocular biometry and to evaluate its associations with refraction in a group of Chinese preschoolers. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 1133 preschoolers 3 to 6 years of age from 8 representative kindergartens. METHODS: Biometric measurements including axial length (AL), anterior chamber depth (ACD), and corneal radius of curvature (CR) were obtained from partial-coherence laser interferometry (IOL Master; Carl Zeiss Meditec, Oberkochen, Germany) before cycloplegia. Lens power (LP) and AL-to-CR ratio were calculated. Cycloplegic refraction (3 drops of 1% cyclopentolate) was measured using an autorefractor (KR8800; Topcon Corp., Tokyo, Japan), and spherical equivalent refraction (SER) was calculated. Biometric and refractive parameters were assessed as a function of age and gender. Multiple regression analysis was performed to explore the associations between refraction and ocular biometry. MAIN OUTCOME MEASURES: Ocular biometric distributions and their relationships to refraction. RESULTS: Among the 1127 children (99.5%) with successful cycloplegic refraction, mean SER was 1.37±0.63 diopters (D). Prevalence of myopia increased from 0% at 3 years of age to 3.7% (95% confidence interval, 1.0%-6.5%) at 6 years of age. Biometric parameters followed Gaussian distributions with means of 22.39±0.68 mm for AL, 7.79±0.25 mm for CR, and 24.61±1.42 D for calculated LP; and non-Gaussian distributions with means of 3.34±0.24 mm for ACD and 2.88±0.06 for AL-to-CR ratio. Axial length, ACD, and AL-to-CR ratio increased from 3 to 6 years of age, CR remained stable, whereas LP declined. Overall, SER declined slightly. For the SER variance, AL explained 18.6% and AL-to-CR ratio explained 39.8%, whereas AL, CR, and LP accounted for 80.0% after adjusting for age and gender. CONCLUSIONS: Young Chinese children are predominantly mildly hyperopic, with a low prevalence of myopia by the age of 6 years. An increase of 1 mm in AL was associated with only 0.45 D of myopic change. Decreases in LP reduce the myopic shifts that normally would be associated with increases in AL, and thus play a key role in refractive development in this age group.

Three-Dimensional Eye Shape, Myopic Maculopathy, and Visual Acuity: The Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.

PURPOSE: To investigate the relationship among eye shape, myopic maculopathy, and visual acuity in highly myopic eyes using 3-dimensional (3D) magnetic resonance imaging (MRI). DESIGN: Observational case series. PARTICIPANTS: The study included 190 eyes of 95 participants with bilateral high myopia from the Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study, with spherical power ≤-6.00 diopters (D) in both eyes. METHODS: The participants underwent best-corrected visual acuity (BCVA), fundus photography, cycloplegic refraction, and ocular biometry. Posterior staphyloma was identified with 3D MRI, and ocular shapes were categorized into spheroidal, ellipsoidal, conical, nasally distorted, temporally distorted, and barrel shapes according to the inferior view from T2-weighted 3D MRI (Achieva 3.0T; Philips Medical Systems, Best, the Netherlands). Myopic maculopathy was graded as C0 to C4 according to the International Photographic Classification and Grading System using fundus photography. The statistical significance of the differences in distribution of myopic maculopathy and BCVA in eyes with different ocular shapes was determined using Pearson's chi-square tests. MAIN OUTCOME MEASURES: Distributions of myopic maculopathy and BCVA in relation to different eye shapes. RESULTS: The mean spherical equivalent and axial length were -11.74±4.10 D and 28.18±1.73 mm in the right eyes, respectively. The same ocular shapes were observed in both eyes in 69 participants (72.6%). The predominant shape was spheroidal (53.7%), followed by nasally distorted and conical types (both 14.7%). C2 and above myopic maculopathy was observed in all barrel-shaped eyes, in 75% temporally distorted eyes, and in 71.4% nasally distorted and conical eyes. In eyes with posterior staphyloma (n = 22), 18 (81.8%) had C2 and above myopic maculopathy compared with 40 eyes (54.8%) without posterior staphyloma (n = 73). Eyes with temporal and nasal distortion, and eyes with staphyloma were more likely to have BCVA <20/40. CONCLUSIONS: Not all highly myopic eyes are deformed. Spheroid was the predominant ocular shape in this series of young patients with high myopia bilaterally. Barrel-shaped and temporally distorted eyes present significant myopic maculopathy, whereas eyes with posterior staphyloma display more severe chorioretinal atrophy. Eyes of more deformed shapes tend to have more severe myopic maculopathy and worse BCVA.

Green spaces and spectacles use in schoolchildren in Barcelona.

Myopia is one of the major causes of low visual acuity during childhood, and hence of the need for spectacles. It is generally more prevalent in urban areas where children are often less exposed to green spaces than in rural areas. This study evaluated the association between exposure to green space and use of spectacles (as a surrogate measure for myopia) in a cohort of 2727 schoolchildren (7-10 years old) recruited from 39 primary schools in Barcelona (2012-2015). We assessed exposure to green spaces by characterizing outdoor surrounding greenness at home and school and during commuting using satellite data on greenness (Normalized Difference Vegetation Index). We also obtained data on the annual average time children spent playing in green spaces through questionnaires. Cross-sectional analyses were conducted based on prevalent cases of spectacles use at baseline data collection campaign and longitudinal analyses based on incident cases of spectacles use during the three-year period between the baseline and last data collection campaigns. An interquartile range (IQR) increase in exposure to green space at home (500m buffer) and school and during commuting was associated with respectively 14% (95% CI: 2%, 26%), 27% (95% CI: 6%, 44%), and 20% (95% CI: 5%, 33%) decrease in spectacles use in cross-sectional analyses. In longitudinal analyses, we observed a reduction of 23% (95% CI: 4%, 39%) and 34% (95% CI: 2%, 55%) associated with an IQR increase in greenness at home and school, respectively. Moreover, an IQR increase in time playing in green spaces was associated with a 28% (95% CI: 7%, 45%) reduction in the risk of spectacles use in the longitudinal analysis. Our observed reduced risk of spectacles use associated with higher contact with green space calls for more refined studies of the association between green spaces and refractive errors of visions.

EPIDEMIC OF PATHOLOGIC MYOPIA: What Can Laboratory Studies and Epidemiology Tell Us?

PURPOSE: To systematically review epidemiologic and laboratory studies on the etiology of high myopia and its links to pathologic myopia. METHODS: Regular Medline searches have been performed for the past 20 years, using "myopia" as the basic search term. The abstracts of all articles have been scrutinized for relevance, and where necessary, translations of articles in languages other than English were obtained. RESULTS: Systematic review shows that there is an epidemic of myopia and high myopia in young adults in East and Southeast Asia, with similar but smaller trends in other parts of the world. This suggests an impending epidemic of pathologic myopia. High myopia in young adults in East and Southeast Asia is now predominantly associated with environmental factors, rather than genetic background. Recent clinical trials show that the onset of myopia can be reduced by increasing the time children spend outdoors, and methods to slow the progression of myopia are now available. CONCLUSION: High myopia is now largely associated with environmental factors that have caused the epidemic of myopia in East and Southeast Asia. An important clinical question is whether the pathologic consequences of acquired high myopia are similar to those associated with classic genetic high myopia. Increased time outdoors can be used to slow the onset of myopia, whereas methods for slowing progression are now available clinically. These approaches should enable the current epidemics of myopia and high myopia to be turned around, preventing an explosion of pathologic myopia.

What Public Policies Should Be Developed to Deal with the Epidemic of Myopia?

Developed countries in East and Southeast Asia are now faced with a high prevalence of high myopia in young adults, and this trend is emerging in other parts of the world. This is likely to lead to increased levels of pathological myopia. Fortunately, several school-based clinical trials have demonstrated that interventions based on increasing the amount of time that children spend outdoors can significantly slow the onset of myopia. I argue that it is time to implement mandatory programs of this kind in school systems, within a framework of regular monitoring of visual acuity, so that those children who become myopic are referred for clinical treatment as soon as possible to slow progression of their myopia towards high and potentially pathological myopia.

Prevalence of Amblyopia in School-Aged Children and Variations by Age, Gender, and Ethnicity in a Multi-Country Refractive Error Study.

PURPOSE: To estimate the age-, gender-, and ethnicity-specific prevalence of amblyopia in children aged 5 to 15 years using data from the multi-country Refractive Error Study in Children (RESC). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Among 46 260 children aged 5 to 15 years who were enumerated from 8 sites in the RESC study, 39 551 had a detailed ocular examination and a reliable visual acuity (VA) measurement in 1 or both eyes. Information on ethnicity was available for 39 321 of these participants. This study focused on findings from the 39 321 children. METHODS: The examination included VA measurements, evaluation of ocular alignment and refractive error under cycloplegia, and examination of the external eye, anterior segment, media, and fundus. MAIN OUTCOME MEASURES: The proportion of children aged 5 to 15 years with amblyopia in different ethnic cohorts. Amblyopia was defined as best-corrected visual acuity (BCVA) of ≤20/40 in either eye, with tropia, anisometropia (≥2 spherical equivalent diopters [D]), or hyperopia (≥+6 spherical equivalent D), after excluding children with fundus or anterior segment abnormalities. RESULTS: The overall prevalence of amblyopia was 0.74% (95% confidence interval, 0.64-0.83) with significant (P < 0.001) variation across ethnic groups: 1.43% in Hispanic, 0.93% in Chinese, 0.62% in Indian, 0.52% in Malay, 0.35% in Nepali, and 0.28% in African children. Amblyopia was not associated with age or gender. The most common cause of amblyopia was anisometropia. CONCLUSIONS: In this study, the prevalence of amblyopia varied with ethnicity and was highest in Hispanic children and lowest in African children. Most cases were unilateral and developed before the age of 5 years. The impact of changes of definitions on prevalence estimates is discussed.

Effect of Time Spent Outdoors at School on the Development of Myopia Among Children in China: A Randomized Clinical Trial.

IMPORTANCE: Myopia has reached epidemic levels in parts of East and Southeast Asia. However, there is no effective intervention to prevent the development of myopia. OBJECTIVE: To assess the efficacy of increasing time spent outdoors at school in preventing incident myopia. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized trial of children in grade 1 from 12 primary schools in Guangzhou, China, conducted between October 2010 and October 2013. INTERVENTIONS: For 6 intervention schools (n = 952 students), 1 additional 40-minute class of outdoor activities was added to each school day, and parents were encouraged to engage their children in outdoor activities after school hours, especially during weekends and holidays. Children and parents in the 6 control schools (n = 951 students) continued their usual pattern of activity. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the 3-year cumulative incidence rate of myopia (defined using the Refractive Error Study in Children spherical equivalent refractive error standard of ≤-0.5 diopters [D]) among the students without established myopia at baseline. Secondary outcome measures were changes in spherical equivalent refraction and axial length among all students, analyzed using mixed linear models and intention-to-treat principles. Data from the right eyes were used for the analysis. RESULTS: There were 952 children in the intervention group and 951 in the control group with a mean (SD) age of 6.6 (0.34) years. The cumulative incidence rate of myopia was 30.4% in the intervention group (259 incident cases among 853 eligible participants) and 39.5% (287 incident cases among 726 eligible participants) in the control group (difference of -9.1% [95% CI, -14.1% to -4.1%]; P < .001). There was also a significant difference in the 3-year change in spherical equivalent refraction for the intervention group (-1.42 D) compared with the control group (-1.59 D) (difference of 0.17 D [95% CI, 0.01 to 0.33 D]; P = .04). Elongation of axial length was not significantly different between the intervention group (0.95 mm) and the control group (0.98 mm) (difference of -0.03 mm [95% CI, -0.07 to 0.003 mm]; P = .07). CONCLUSIONS AND RELEVANCE: Among 6-year-old children in Guangzhou, China, the addition of 40 minutes of outdoor activity at school compared with usual activity resulted in a reduced incidence rate of myopia over the next 3 years. Further studies are needed to assess long-term follow-up of these children and the generalizability of these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00848900.

Myopia.

Myopia has emerged as a major health issue in east Asia, because of its increasingly high prevalence in the past few decades (now 80-90% in school-leavers), and because of the sight-threatening pathologies associated with high myopia, which now affects 10-20% of those completing secondary schooling in this part of the world. Similar, but less marked, changes are occurring in other parts of the world. The higher prevalence of myopia in east Asian cities seems to be associated with increasing educational pressures, combined with life-style changes, which have reduced the time children spend outside. There are no reported major genes for school myopia, although there are several genes associated with high myopia. Any genetic contribution to ethnic differences may be small. However, to what extent many genes of small effect and gene-environment interactions contribute to variations in school myopia within populations remains to be established. There are promising optical and pharmacological interventions for preventing the development of myopia or slowing its progression, which require further validation, and promising vision-sparing treatments for pathological myopia.

Risk factors for incident myopia in Australian schoolchildren: the Sydney adolescent vascular and eye study.

PURPOSE: To examine the risk factors for incident myopia in Australian schoolchildren. DESIGN: Population-based, longitudinal cohort study. PARTICIPANTS: The Sydney Adolescent Vascular and Eye Study (SAVES) was a 5- to 6-year follow-up of the Sydney Myopia Study (SMS). At follow-up, 2103 children were reexamined: 892 (50.5%) from the younger cohort and 1211 (51.5%) from the older cohort. Of these, 863 in the younger cohort and 1196 in the older cohort had complete refraction data. METHODS: Cycloplegic autorefraction (cyclopentolate 1%; Canon RK-F1; Canon, Tokyo, Japan) was measured at baseline and follow-up. Myopia was defined as a spherical equivalent refraction of ≤-0.50 diopters (D). Children were classified as having incident myopia if they were nonmyopic at baseline and myopic in either eye at follow-up. A comprehensive questionnaire determined the amount of time children spent outdoors and doing near work per week at baseline, as well as ethnicity, parental myopia, and socioeconomic status. MAIN OUTCOME MEASURES: Incident myopia. RESULTS: Children who became myopic spent less time outdoors compared with children who remained nonmyopic (younger cohort, 16.3 vs. 21.0 hours, respectively, P<0.0001; older cohort, 17.2 vs. 19.6 hours, respectively, P=0.001). Children who became myopic performed significantly more near work (19.4 vs. 17.6 hours; P=0.02) in the younger cohort, but not in the older cohort (P=0.06). Children with 1 or 2 parents who were myopic had greater odds of incident myopia (1 parent: odds ratio [OR], 3.2, 95% confidence interval [CI], 1.9-5.2; both parents: OR, 3.3, 95% CI, 1.6-6.8) in the younger but not the older cohort. Children of East Asian ethnicity had a higher incidence of myopia compared with children of European Caucasian ethnicity (both P<0.0001) and spent less time outdoors (both P<0.0001). A less hyperopic refraction at baseline was the most significant predictor of incident myopia. The addition of time outdoors, near work, parental myopia, and ethnicity to the model significantly improved the predictive power (P<0.0001) in the younger cohort but had little effect in the older cohort. CONCLUSIONS: Time spent outdoors was negatively associated with incident myopia in both age cohorts. Near work and parental myopia were additional significant risk factors for myopia only in the younger cohort. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence and 5- to 6-year incidence and progression of myopia and hyperopia in Australian schoolchildren.

PURPOSE: To determine the prevalence, incidence, and change in refractive errors for Australian schoolchildren and examine the impact of ethnicity and sex. DESIGN: Population-based cohort study. PARTICIPANTS: The Sydney Adolescent Vascular and Eye Study, a 5- to 6-year follow-up of the Sydney Myopia Study, examined 2760 children in 2 age cohorts, 12 and 17 years. Longitudinal data were available for 870 and 1202 children in the younger and older cohorts, respectively. METHODS: Children completed a comprehensive examination, including cycloplegic autorefraction (cyclopentolate 1%; Canon RK-F1). Myopia was defined as ≤-0.50 diopters (D) and hyperopia as ≥+2.00 D right eye spherical equivalent refraction. MAIN OUTCOME MEASURES: Baseline and follow-up refraction. RESULTS: Prevalence of myopia increased between baseline and follow-up for both the younger (1.4%-14.4%; P<0.0001) and older cohorts (13.0%-29.6%; P<0.0001). The annual incidence of myopia was 2.2% in the younger cohort and 4.1% in the older. Children of East Asian ethnicity had a higher annual incidence of myopia (younger 6.9%, older 7.3%) than European Caucasian children (younger 1.3%, older 2.9%; all P<0.0001). The prevalence of myopia in European Caucasian children almost doubled between the older (4.4%; 95% confidence interval [CI], 3.0-5.8) and younger samples (8.6%; 95% CI, 6.7-10.6) when both were aged 12 years. Children with ametropia at baseline were more likely to have a significant shift in refraction (hyperopia: odds ratio [OR], 3.4 [95% CI, 1.2-9.8]; myopia: OR, 6.3 [95% CI, 3.7-10.8]) compared with children with no refractive error. There was no significant difference in myopia progression between children of European Caucasian and East Asian ethnicity (P = 0.7). CONCLUSIONS: In Sydney, myopia prevalence (14.4%, 29.6%) and incidence (2.2%, 4.1%) was low for both age cohorts, compared with other locations. However, in European Caucasian children at age 12, the significantly higher prevalence of myopia in the younger sample suggests a rise in prevalence, consistent with international trends. Progression of myopia was similar for children of East Asian and European Caucasian ethnicity, but lower than reported in children of East Asian ethnicity in East Asia, suggesting that environmental differences may have some impact on progression.

Time outdoors and the prevention of myopia.

Recent epidemiological evidence suggests that children who spend more time outdoors are less likely to be, or to become myopic, irrespective of how much near work they do, or whether their parents are myopic. It is currently uncertain if time outdoors also blocks progression of myopia. It has been suggested that the mechanism of the protective effect of time outdoors involves light-stimulated release of dopamine from the retina, since increased dopamine release appears to inhibit increased axial elongation, which is the structural basis of myopia. This hypothesis has been supported by animal experiments which have replicated the protective effects of bright light against the development of myopia under laboratory conditions, and have shown that the effect is, at least in part, mediated by dopamine, since the D2-dopamine antagonist spiperone reduces the protective effect. There are some inconsistencies in the evidence, most notably the limited inhibition by bright light under laboratory conditions of lens-induced myopia in monkeys, but other proposed mechanisms possibly associated with time outdoors such as relaxed accommodation, more uniform dioptric space, increased pupil constriction, exposure to UV light, changes in the spectral composition of visible light, or increased physical activity have little epidemiological or experimental support. Irrespective of the mechanisms involved, clinical trials are now underway to reduce the development of myopia in children by increasing the amount of time they spend outdoors. These trials would benefit from more precise definition of thresholds for protection in terms of intensity and duration of light exposures. These can be investigated in animal experiments in appropriate models, and can also be determined in epidemiological studies, although more precise measurement of exposures than those currently provided by questionnaires is desirable.